Treosulfan-based Conditioning for Transplantation in AML/MDS

Sponsor

Dr. Avichai Shimoni MD (Other)

Overall Status

Completed

CT.gov ID

NCT00491634

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study hypotheses is that the introduction of dose escalated treosulfan, in substitution to busulfan, will reduce toxicity after allogeneic transplantation while improving myeloablation and and disease control in patients with AML and MDS not eligible for standard transplantation.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome	Drug: treosulfan Drug: Treosulfan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Chemo-refractory or Previously Untreated Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 treosulfan	Drug: treosulfan 12 g/m2 x 3 days Drug: Treosulfan 12 g/m2 x 3

Arm

Intervention/Treatment

Experimental: 1

treosulfan

Drug: treosulfan

12 g/m2 x 3 days

Drug: Treosulfan

12 g/m2 x 3

Outcome Measures

Primary Outcome Measures

disease-free survival [2 years after transplantation]

Secondary Outcome Measures

treatment-related mortality, GVHD, relapse, overall survival [2 year after transplantation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 68 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age less than physiologic 68 years.
Patients with AML and MDS not eligible for standard TBI- or Busulfan-based myeloablative conditioning due to age, concurrent medical condition, or extensive prior therapy (e.g. age > 55 years for HLA-matched sibling transplants or > 50 for matched unrelated donor transplants, prior / concomitant pulmonary, liver, or other organ complications).
This study will only include patients with chemo-refractory disease or previously untreated active disease.

acute myeloid leukemias (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at diagnosis) in induction failure, PR, untreated or chemo-refractory relapse. Patients must have > 10% marrow blasts at the time of transplantation.
myelodysplastic syndromes (MDS) according to WHO classification (< 20% myeloblasts in peripheral blood and bone marrow at diagnosis), indicated for allogeneic transplantation:

refractory anaemia with excess blasts (RAEB-1 and RAEB-2) with no prior therapy

Patients must have an HLA matched related or unrelated donor willing to donate either peripheral blood stem cells or bone marrow. Matching is based on high-resolution class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB1) typing. The goal is to transplant > 3 x 106 CD34+ cells per kg body weight of the recipient -

Exclusion Criteria:

Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
Creatinine > 2.0 mg/dl
ECOG-Performance status > 2
Uncontrolled infection
Pregnancy or lactation
Abnormal lung diffusion capacity (DLCO < 40% predicted)
Severe cardiovascular disease
CNS disease involvement
Pleural effusion or ascites > 1 liter
Known hypersensitivity to fludarabine or treosulfan
Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate -